tbuckley/cabot-search huggingface dataset:
Randomized Controlled Clinical Trials
Authors: David H. Spodick
Journal: JAMA (1982)

THE RANDOMIZED controlled clinical trial (RCT) has become the accepted standard for demonstrating the true therapeutic effects in evaluating most forms of treatment. Its scientific and ethical bases are well established. Yet it is standard practice, at least for trials of new pills and injections, to take certain decisions out of physicians' hands by "blinding" and by randomization, letting chance rather than prejudice decide which patients get the trial treatment. This is partly because physicians' behavior has consistently been heavily biased in relation to therapeutic trials. A flagrant expression is found in the schizoid behavior of journal reviewers and institutional committees that insist on high standards of proof for pills and low standards for surgical procedures. Indeed, an important reason for the existence of the Food and Drug Administration is to ensure optimum scientific and ethical behavior in assessing the efficacy and safety of new medicines. (There is no FDA
A Text-Book of Medical Diagnosis.
Journal: JAMA (1926)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Knee and Related Structures: Injuries—Deformities—Diseases— Disabilities.
Journal: JAMA (1952)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Criteria for the Diagnosis of Alcoholism
Authors: Frank A. Seixas
Journal: JAMA (1972)

It has been a historic mission of national voluntary health organizations to provide diagnostic and classificatory standards for the diseases in which their interest lies. Thus we have the Jones Criteria for rheumatic fever, the American Heart Association's criteria for classifying heart disease and, more recently, kidney disease, the diagnostic classification for tuberculosis developed by the American Tuberculosis and Respiratory Disease Association, and many others. One disease that up to now has not had this kind of attention has been alcoholism, and the need for clarification of what we mean when a diagnosis of alcoholism is to be made has been urgent. The need is exemplified by the statement in the Supreme Court case, Powell vs Texas, which held that there was no "substantial consensus as to the 'manifestations of alcoholism.'" It turns out that it has been possible to obtain a rather strong agreement as to the meanings and
Rapid Assay of Murine Leukemia Virus Helper Activity for Friend Spleen Focus-Forming Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Steeves, R. A., Eckner, R. J., Mirand, E. A., Priore, R. L.
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Rapid Assay of Murine Leukemia Virus Helper Activity for Friend Spleen Focus-Forming Virus Get access R. A. Steeves, R. A. Steeves Department of Experimental Biology, Roswell Park Memorial Institute, Buffalo, New York 14203 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. J. Eckner, R. J. Eckner Department of Experimental Biology, Roswell Park Memorial Institute, Buffalo, New York 14203 Search for other works by this author on: Oxford Academic PubMed Google Scholar E. A. Mirand, E. A. Mirand Department of Experimental Biology, Roswell Park Memorial Institute, Buffalo, New York 14203 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. L. Priore R. L. Priore Department of Experimental Biology, Roswell Park Memorial Institute, Buffalo, New York 14203 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 46, Issue 6, June 1971, Pages 1219–1228, https://doi.org/10.1093/jnci/46.6.1219 Published: 01 June 1971 Article history Received: 24 November 1970 Accepted: 24 February 1971 Published: 01 June 1971
Nifedipine for Hypertensive Emergencies
Authors: Gary L. Fanning
Journal: JAMA (1997)

<h3>To the Editor.</h3> —As an anesthesiologist in a freestanding ophthalmologic surgery center, I have administered approximately 12 500 peribulbar blocks to patients undergoing cataract surgery during the past 5 years. In my practice, hypertension is a frequently encountered problem (nearly half of my patients are taking medications for hypertension) that I cannot leave untreated. Because of potentially devastating hemorrhagic complications that may accompany peribulbar blocks and intraocular surgery, it is not prudent to begin surgical treatment until the patient's blood pressure is under control. Because more than 90% of the patients with hypertension whom I manage have had blood pressures recorded in the normal range in their physicians' offices during their preoperative evaluations, I cannot justify sending them back to their physicians for more aggressive treatment. Consequently, I have administered oral nifedipine (5-10 mg) to nearly 30% of my patients to maintain their systolic blood pressures at less than 170 mm Hg prior
Thyroglossal Duct Carcinoma
Authors: Manfred Blum
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The report by Chandrasoma and Janssen (1982;247:1406) of a thyroglossal cyst lined by gastric epithelium is intriguing from an embryologic and a clinical perspective. However, we wish to indicate that thyroglossal cysts are not "universally benign" as claimed. The literature contains reference to some 90 examples of carcinoma in the thyroglossal tract, mostly of the papillary type.<sup>1-5</sup>In as many as 25% of cases, carcinoma may be present elsewhere in the thyroid gland.<sup>3</sup>The prognosis for patients with this neoplasm appears to be excellent,<sup>2</sup>but recently a fatality due to anaplastic carcinoma that arose in a thyroglossal duct remnant was reported.<sup>5</sup>Since seven patients with this disorder were observed in our institution during the past ten years<sup>2</sup>(additional manuscript submitted for publication), it is possible to speculate that a malignant neoplasm in a thyroglossal duct actually may not be terribly rare.
Preoperative Autologous Blood Donations Before Elective Hysterectomy
Authors: Michael H. Kanter
Journal: JAMA (1996)

<h3>Objective.</h3> —To determine whether preoperative autologous blood donation is justified for patients undergoing elective abdominal or vaginal hysterectomy. <h3>Design.</h3> —Retrospective cohort study. <h3>Patients and Setting.</h3> —A total of 263 consecutive patients admitted for elective abdominal or vaginal hysterectomy to a community health maintenance organization hospital during 1993 and 1994. <h3>Main Outcome Measures.</h3> —Evaluation of transfusion rates for patients who did and did not donate autologous blood; determination of any risk factors that would predict the need for transfusion; and evaluation of the need for transfusion based on chart review. <h3>Results.</h3> —Of 263 patients, 26 received a blood transfusion. The major risk factor identified for transfusion was the donation of autologous blood. Of 140 patients who donated autologous blood, 25 were transfused, whereas just 1 patient of 123 who did not donate autologous blood was transfused (P&lt;.001). Patients who donated autologous blood had significantly lower mean admission hemoglobin level than patients who did not donate (119 g/L vs 132 g/L; P&lt;.05); logistic regression showed that autologous donation was an independent risk factor for transfusion. <h3>&gt;Conclusion.</h3> —For hysterectomy patients, donation of autologous blood causes anemia and is associated with a more liberal transfusion policy. These 2 factors result in a markedly increased incidence of transfusion with its associated risks. Elimination of preoperative autologous donation for these patients should not result in frequent exposure to allogeneic blood.
The neurobiology of long COVID
Authors: Michelle Monje, Akiko Iwasaki
Journal: Neuron (2022)

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID-19 syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impact on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.
Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers
Authors: Lei Zhang, Biwei Ye, Zhuo Chen, Zhe-Sheng Chen
Journal: Acta Pharmaceutica Sinica B (2022)

Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein–protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.
Loss of Heterozygosity Spectrum Depends on Ploidy Level in Natural Yeast Populations
Authors: Abhishek Dutta, Fabien Dutreux, Joseph Schacherer
Journal: Molecular Biology and Evolution (2022)

Abstract The appearance of genomic variations such as loss of heterozygosity (LOH) has a significant impact on phenotypic diversity observed in a population. Recent large-scale yeast population genomic surveys have shown a high frequency of these events in natural isolates and more particularly in polyploids. However, the frequency, extent, and spectrum of LOH in polyploid organisms have never been explored and are poorly characterized to date. Here, we accumulated 5,163 LOH events over 1,875 generations in 76 mutation accumulation (MA) lines comprising nine natural heterozygous diploid, triploid, and tetraploid natural S. cerevisiae isolates from different ecological and geographical origins. We found that the rate and spectrum of LOH are variable across ploidy levels. Of the total accumulated LOH events, 8.5%, 21%, and 70.5% of them were found in diploid, triploid, and tetraploid MA lines, respectively. Our results clearly show that the frequency of generated LOH events increases with ploidy level. In fact, the cumulative LOH rates were estimated to be 9.3 × 10−3, 2.2 × 10−2, and 8.4 × 10−2 events per division for diploids, triploids, and tetraploids, respectively. In addition, a clear bias toward the accumulation of interstitial and short LOH tracts is observed in triploids and tetraploids compared with diploids. The variation of the frequency and spectrum of LOH events across ploidy level could be related to the genomic instability, characterizing higher ploidy isolates.
A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles
Authors: Tamás Raskó, Amit Pande, Kathrin Radscheit, Annika Zink, Manvendra Singh, Christian Sommer, Gerda Wachtl, Orsolya Kolacsek, Gizem Inak, Attila Szvetnik, Spyros Petrakis, Mario Bunse, Vikas Bansal, Matthias Selbach, Tamás I Orbán, Alessandro Prigione, Laurence D Hurst, Zsuzsanna Izsvák
Journal: Molecular Biology and Evolution (2022)

Although new genes can arrive from modes other than duplication, few examples are well characterized. Given high expression in some human brain subregions and a putative link to psychological disorders [e.g., schizophrenia (SCZ)], suggestive of brain functionality, here we characterize piggyBac transposable element-derived 1 (PGBD1). PGBD1 is nonmonotreme mammal-specific and under purifying selection, consistent with functionality. The gene body of human PGBD1 retains much of the original DNA transposon but has additionally captured SCAN and KRAB domains. Despite gene body retention, PGBD1 has lost transposition abilities, thus transposase functionality is absent. PGBD1 no longer recognizes piggyBac transposon-like inverted repeats, nonetheless PGBD1 has DNA binding activity. Genome scale analysis identifies enrichment of binding sites in and around genes involved in neuronal development, with association with both histone activating and repressing marks. We focus on one of the repressed genes, the long noncoding RNA NEAT1, also dysregulated in SCZ, the core structural RNA of paraspeckles. DNA binding assays confirm specific binding of PGBD1 both in the NEAT1 promoter and in the gene body. Depletion of PGBD1 in neuronal progenitor cells (NPCs) results in increased NEAT1/paraspeckles and differentiation. We conclude that PGBD1 has evolved core regulatory functionality for the maintenance of NPCs. As paraspeckles are a mammal-specific structure, the results presented here show a rare example of the evolution of a novel gene coupled to the evolution of a contemporaneous new structure.
Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer
Authors: Xueli Tian, Rui Wang, Tingxuan Gu, Fayang Ma, Kyle Vaughn Laster, Xiang Li, Kangdong Liu, Mee-Hyun Lee, Zigang Dong
Journal: Molecular Cancer (2022)

Abstract EGFR-TKI targeted therapy is one of the most effective treatments for lung cancer patients harboring EGFR activating mutations. However, inhibition response is easily attenuated by drug resistance, which is mainly due to bypass activation or downstream activation. Herein, we established osimertinib-resistant cells by stepwise dose-escalation in vitro and an osimertinib-resistant patient-derived xenograft model through persistent treatment in vivo. Phosphorylated proteomics identified that MEK1 and AKT1/2 were abnormally activated in resistant cells compared with parental cells. Likewise, EGFR inhibition by osimertinib induced activation of MEK1 and AKT1/2, which weakened osimertinib sensitivity in NSCLC cells. Consequently, this study aimed to identify a novel inhibitor which could suppress resistant cell growth by dual targeting of MEK1 and AKT1/2. Based on computational screening, we identified that costunolide could interact with MEK1 and AKT1/2. Further exploration using in vitro kinase assays validated that costunolide inhibited the kinase activity of MEK1 and AKT1/2, which restrained downstream ERK-RSK2 and GSK3β signal transduction and significantly induced cell apoptosis. Remarkably, the combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.
Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy
Authors: Yuemin Wang, Duan Wang, Yuyue Zhang, Hong Xu, Luxuan Shen, Jing Cheng, Xinyuan Xu, Hong Tan, Xingyu Chen, Jianshu Li
Journal: Bioactive Materials (2022)

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform ([email protected]2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of [email protected]2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.
Learning networks in the pandemic: mobilising evidence for improvement
Authors: Manbinder S Sidhu, Gary A Ford, Naomi J Fulop, C Michael Roberts
Journal: BMJ (2022)

<h3>Abstract</h3> The ability to visualize small moving objects is vital for the survival of many animals, as these could represent predators or prey. For example, predatory insects, including dragonflies, robber flies and killer flies, perform elegant, high-speed pursuit of both biological and artificial targets. Many non-predatory insects, including male hoverflies and blowflies, also pursue targets during territorial or courtship interactions. Such predatory and non-predatory pursuits are often guided by heuristic rules based on the target image’s retinal size, retinal speed, or both. To date, most hoverfly pursuits were studied outdoors. To investigate naturalistic hoverfly (<i>Eristalis tenax</i>) pursuits under more controlled settings, we constructed an indoor arena that was large enough to encourage naturalistic behavior. We presented artificial beads of different sizes, moving at different speeds, and filmed the pursuits with two cameras, allowing subsequent 3D reconstruction. Using this technique, we show that male <i>E. tenax</i> hoverflies are unlikely to use strict heuristic rules based on retinal size or speed to initiate pursuit, at least in our indoor setting. We show that male <i>E. tenax</i> start pursuits of beads that are moving either above or below them. Furthermore, we show that target pursuit behavior can be broken down into two stages. In the first stage the hoverfly attempts to decrease the distance to the target by flying at high speed. During the second stage the hoverfly’s forward speed is correlated with the speed of the bead, so that it remains close to the bead without catching it. This could be useful for gathering more information before physical interaction.
Acute infections in people who inject drugs
Authors: Neil Stevenson, Stuart Suttie, Eduardo Fernandes, Nikolas Rae
Journal: BMJ (2022)

<h3>Background</h3> SLE is an independent risk factor for cardiovascular disease (CVD). This study aimed to determine which among QRISK2, QRISK3, Framingham Risk Score (FRS), modified Framingham Risk Score (mFRS) and SLE Cardiovascular Risk Equation (SLECRE) best predicts CVD. <h3>Methods</h3> This is a single-centre analysis on 1887 patients with SLE followed prospectively according to a standard protocol. Tools’ scores were evaluated against CVD development at/within 10 years for patients with CVD and without CVD. For patients with CVD, the index date for risk score calculation was chosen as close to 10 years prior to CVD event. For patients without CVD, risk scores were calculated as close to 10 years prior to the most recent clinic appointment. Proportions of low-risk (&lt;10%), intermediate-risk (10%–20%) and high-risk (&gt;20%) patients for developing CVD according to each tool were determined, allowing sensitivity, specificity, positive/negative predictive value and concordance (c) statistics analysis. <h3>Results</h3> Among 1887 patients, 232 CVD events occurred. QRISK2 and FRS, and QRISK3 and mFRS, performed similarly. SLECRE classified the highest number of patients as intermediate and high risk. Sensitivities and specificities were 19% and 93% for QRISK2, 22% and 93% for FRS, 46% and 83% for mFRS, 47% and 78% for QRISK3, and 61% and 64% for SLECRE. Tools were similar in negative predictive value, ranging from 89% (QRISK2) to 92% (SLECRE). FRS and mFRS had the greatest c-statistics (0.73), while QRISK3 and SLECRE had the lowest (0. 67). <h3>Conclusion</h3> mFRS was superior to FRS and was not outperformed by the QRISK tools. SLECRE had the highest sensitivity but the lowest specificity. mFRS is an SLE-adjusted practical tool with a simple, intuitive scoring system reasonably appropriate for ambulatory settings, with more research needed to develop more accurate CVD risk prediction tools in this population.
Molecular mechanism(s) of regulations of cancer stem cell in brain cancer propagation
Authors: Kumari Swati, Kirti Agrawal, Sibi Raj, Rajeev Kumar, Anand Prakash, Dhruv Kumar
Journal: Medicinal Research Reviews (2022)

Abstract Brain tumors are most often diagnosed with solid neoplasms and are the primary reason for cancer‐related deaths in both children and adults worldwide. With recent developments in the progression of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. However, the high recurrence rate and high mortality rate remain unresolved and are closely linked to the biological features of cancer stem cells (CSCs). Research on tumor biology has reached a new age with more understanding of CSC features. CSCs, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Therefore, in the diagnosis and treatment of tumors, recognizing the biological properties of CSCs is of considerable significance. Here, we have discussed the concept of CSCs and their significant role in brain cancer growth and propagation. We have also discussed personalized therapeutic development and immunotherapies for brain cancer by specifically targeting CSCs.